Associations between vitamin D and autoimmune diseases: Mendelian randomization analysis

Area of Science:

• Nutritional Immunology
• Genetic Epidemiology
• Autoimmune Diseases

Background:

• The VITAL trial indicated a potential protective role for vitamin D in autoimmune diseases, but further investigation is needed.
• Uncertainties persist regarding the causal relationship between vitamin D and autoimmune conditions.

Purpose of the Study:

• To investigate the potential causal effects of vitamin D on composite and individual autoimmune diseases using Mendelian randomization.
• To explore the association between genetically predicted vitamin D levels and the risk of autoimmunity and autoinflammation.

Main Methods:

• Utilized UK Biobank data from 332,984 participants, identifying 23,089 with autoimmune diseases.
• Categorized diseases into 'autoimmunity' and 'autoinflammation' subgroups for mechanistic analysis.
• Employed Mendelian randomization with genetic variants linked to vitamin D metabolism and analyzed non-linear effects.

Main Results:

• Genetically predicted vitamin D was associated with a reduced risk of autoinflammation diseases (OR 0.95 per 10 ng/ml increase; P=0.03).
• Significant associations were found for lower risk of psoriasis (OR 0.91; P=0.005) and suggestively for systemic lupus erythematosus (OR 0.84; P=0.08).
• No evidence of a non-linear relationship between vitamin D and autoimmune outcomes was observed.

Conclusions:

• Genetic evidence supports a causal link between 25-hydroxycholecalciferol concentrations and reduced risk of psoriasis and systemic lupus erythematosus.
• Findings have implications for developing disease prevention strategies and refining vitamin D supplementation trial designs.